Ganymed Closes $61M Internal Round for Lead IMAB Program

By Cormac SheridanStaff Writer

The deep-pocketed brothers Thomas and Andreas Strüngmann have signed another big check, leading a €45 million (US$61 million) internal round in Ganymed Pharmaceuticals AG to enable it to take forward its pipeline of “ideal” monoclonal antibodies (IMABs) in cancer indications.

Its lead compound, IMAB362 is undergoing a Phase IIb trial in gastroesophageal cancer, which will report preliminary data next year.

The Mainz, Germany-based firm has an enviable position within European biotechnology, having raised €170 million since it was spun out from the universities of Mainz and Zurich, Switzerland, in 2001 .

Its majority shareholder is ATS Beteiligungsverwaltung GmbH, an investment vehicle of the Strüngmann family, who realized a cash fortune of €5.65 billion from the 2005 sale of generic drugmaker Hexal AG, of Holzkirchen, Germany, and a majority stake in its U.S. affiliate Eon Labs, to Basel, Switzerland-based Novartis AG.

“We did not need to look for new investors,” Ganymed CEO Özlem Türeci told BioWorld Today. “They have a strong commitment to this company.” The other participants in the transaction were MIG Fond and FCPB Gany GmbH.

The company expects recruitment in the three-arm, open-label study of IMAB362 as first-line therapy in gastroesophageal cancer to be completed by next April. The primary endpoint of the 210-patient study is progression-free survival, while overall survival is a secondary endpoint. “The first trends and tendencies will be seen by late summer,” Türeci said.

The final study report will not be available until late 2015, however. If the data are positive, the company aims to be in a position to begin a Phase III study quickly, although it has yet to decide whether it will do so alone or with a partner. “We are in a position where we could perform a Phase III by ourselves, and we are backed to do that by our investors,” Türeci said. Either way, it plans to pursue the study in the U.S. and in Europe.

Several other antibodies have fallen in that indication, including Avastin (bevacizumab, Roche AG) and Erbitux (cetuximab, Eli Lilly and Co.), although Herceptin (trastuzumab, Roche AG) gained approval earlier this year for treating HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

Ganymed’s first clinical readout is as second-line therapy as well. “We already have convincing data from a Phase IIa trial,” Türeci said. According to preliminary data, 20 percent of per-protocol patients (n = 21) with metastatic, refractory or recurrent advanced gastroesophageal adenocarcinomas achieved a partial remission, while another 28 percent had stable disease.

Ganymed’s antibodies have a conventional structure but are directed against targets that are highly specific to cancer cells, which allows for a wider therapeutic window than many other antibodies that are directed at solid tumors. In addition to hitting its intended target, the company is also able to deploy immune-related functions, including induction of apoptosis, antibody-dependent cell-mediated cytotoxicity and antibody-dependent complement cell lysis without excessive toxicity.

IMAB362 is directed against claudin 18 splice variant 2 (claudin 18.2), a tight-junction protein, the expression of which is normally confined to fully differentiated epithelial cells of the gastric mucosa. It is expressed in about 80 percent of gastroesophageal adenocarcinomas and in about 60 percent of pancreatic tumors. The company is developing a companion diagnostic in parallel, Claudetect 18.2, which already has received a European CE mark.

The present Phase IIb study will test whether there is a correlation between high levels of claudin 18.2 expression and clinical benefit from IMAB362.

Ganymed is competing against several big guns in its leading indication. Amgen Inc., of Thousand Oaks, Calif., is in Phase III trials with Rilotumumab (AMG102), which targets the hepatocyte growth factor/scatter factor pathway. Roche AG, of Basel, Switzerland, is conducting Phase III trials of onartuzumab, which targets hepatocyte growth factor receptor, or c-Met.